Disease and the microbiota (2)

Complications due to alcohol: we were not all created equal

For an equivalent intake of alcohol in terms of quantity and duration, only some excessive drinkers will develop liver disease. This “unfairness” may be explained by the fact that each one of us has a specific microbiota, and that it plays a key role in triggering cirrhosis. INRA scientists working with the Université Paris-Sud, AP-HP (the Paris public hospital authority) and Aix-Marseille University wanted to find out for sure. Their studies confirmed, first of all, that the microbiota of patients with alcoholic hepatitis is different from that of drinkers who do not have liver disease. Next, mice were “humanised”, that is, given the microbiota of alcoholics who developed hepatitis, while other mice received a microbiota of alcoholics without liver disease. All the mice were then fed alcohol. The first group quickly developed inflammation of the liver and adipose tissue. These findings showed that it was possible to treat liver lesions in ailing mice by transferring the microbiota of alcoholic mice which never developed liver disease. It is therefore clear that susceptibility to alcoholic liver disease depends largely on the microbiota. Going forward, it is perfectly reasonable to expect to be able to detect people who are susceptible to alcohol toxicity, and even to treat those who develop liver lesions by modifying their microbiota through diet, probiotics, or the transfer of faecal microbiota*.

Cancer: reducing the risk of secondary effects of immunotherapy thanks to intestinal microbiota

Immunotherapy (stimulation of the immune defences of a patient) is now known to be particularly effective in oncology. Tumours shrink, patient lifespan is significantly extended, and there is now a cure for some previously incurable metastatic cancers. But the hidden face of this “therapeutic revolution” remains secondary effects for more than 20% of patients treated. They often include severe inflammatory colitis. In order to better understand the role of the microbiota in immunotherapy and the onset of colitis, studies were carried out by a team of researchers from INRA, the Gustave Roussy Institute, AP-HP (Paris public hospital authority) and the Pasteur Institute. The findings provide valuable lessons. First and foremost, the researchers found that when two clearly-identified bacteria are absent from intestinal microbiota, drugs are no longer effective in combatting tumours. But as soon as these two bacteria are restored in the microbiota of mice, the antibody effect returns. Better yet, these bacteria provoke immune reactions (immunogens), thereby acting as adjuvant treatment in oncology (“oncobiotics”). In humans, the microbiota may well dictate therapeutic response and the efficiency of the anti-cancer drugs, just as the risk of secondary effects could be predetermined for each patient before treatment begins. In the near future, patients with a less-than-ideal microbiota might also benefit from a compensating bacterial combination thanks to prebiotics, immunogen bacteria, or faecal transplants*. Thus, patients could build up a microbiota that is apt at stimulating the anti-tumour effect of immunotherapy and/or that protects them from the harmful effects of cancer treatment.

Chemotherapy: bacteria to the rescue

What if intestinal microbiota stimulated immune response in patients to help them battle cancer over the course of chemotherapy? This is what INRA researchers working with the Gustave Roussy Institute, Inserm and the Pasteur Institute have found. Cyclophosphamide is one of the most commonly used drugs in chemotherapy. But its secondary effects include upsetting the equilibrium of the microbiota and allowing certain bacteria to cross the intestinal barrier and end up in the blood stream and lymph nodes. The human body considers these bacteria, which make their way into blood plasma, harmful, and triggers an immediate immune response. Paradoxically, this chain reaction is actually very useful. The body’s immune response against the bacteria helps patients fight tumours even better, by stimulating other immune defences. Thus, new lymphocytes (which destroy foreign cells) kick in to help those already mobilised by chemotherapy. A winning combination that is very beneficial to the patient.

Microbiota in chickens: salmonella in danger of extinction?

Salmonella. For the public at large, the word conjures up images of gastroenteritis, or even serious food poisoning. But human contamination has been on the wane for years in Europe, falling by 50%. This is owed to epidemiological studies that have shown that to decrease contamination in humans, contamination must first be decreased in farm animals, in particular poultry. Research has focused on two serotypes most often found in humans: Salmonella enteritidis and Salmonella typhimurium. INRA researchers have shown that some genes favour resistance to these bacteria in poultry. Other teams are looking at the key role intestinal microbiota play in resistance to salmonella. Since salmonella gets transmitted through poultry droppings, scientists must, on the one hand, identify the bacteria in the microbiota that determine a weak or strong excretor of salmonella. On the other hand, using gene sequencing, they must identify the microbiota bacteria capable of preventing salmonella from settling into poultry, because when an animal is contaminated, it is already too late.

A prebiotic is made up of dietary fibre that selectively stimulates growth and/or the activity of intestinal bacteria. Prebiotics may influence the health and well-being of the host.

Probiotic

According to the World Health Organisation, a probiotic is a microorganism (bacteria or yeast) which, when administered regularly and in adequate amounts, confers a health benefit on the host beyond its nutritional value.

Faecal transplants

Also called faecal grafting or transfer of faecal microbiota. It is possible to modify gut microbiota by nutritional recommendations or probiotics. In extreme cases, faecal transplants (or grafts) consist of inoculating the microbiota of a healthy donor in the digestive tract of a recipient with a view to redressing imbalances in the intestinal microbiota of the recipient.